Beyond the Reflex Arc: An Evidence-Based Discussion of the Management of Febrile Infants Cole Condra, MD MSc Division of Emergency Medical Services Children s Mercy Hospital October 1, 2011
Disclosure I have no actual or potential conflict of interest in relation to this program
Objectives 1. Describe the primary pathogens/pathology in the febrile neonate and infant 2. Interpret the evaluation of the febrile infant using evidence-based guidelines 3. Distinguish special circumstances regarding the evaluation of febrile infants (RSV, influenza)
Outline Febrile Infant CPG Febrile Neonates Bacteria HSV Febrile Infants Low-Risk Criteria Special Circumstances RSV Influenza
Terminology: Fever Core temperature (rectal) 38.0 o C (100.4 o F) Axillary/tympanic/ pacifier temperatures are unreliable in young children -Baraff. Ann Emerg Med 2000; 36:602-614
Bundling Elevates skin temperature not rectal temperature (N=64) Skin temperature 2.67 o C/hr Rectal temperature 0.06 o C/hr - Grover. Pediatrics 1994; 94:669-673 Fever > 38.0 o C should not be attributed to bundling
Febrile Neonates 0-28 Days: Pathogens Bacterial Listeria monocytogenes Group B streptococcus Escherichia coli Viral Herpes simplex (HSV) Enterovirus (EV)
Febrile Neonates No criteria exist to safely identify febrile neonates as low-risk for serious bacterial infections (SBI) All febrile neonates require full sepsis evaluation with inpatient antibiotics regardless of clinical appearance Perhaps 1 exception (RSV)
Herpes Simplex (HSV) Must be considered in infants 28 days who have any of the following: Are ill-appearing Have mucocutaneous vesicles Have neurologic symptoms (seizures) Have CSF pleocytosis with a negative Gram stain Lethargy correlates with CNS infection Elevated liver enzymes correlate with disseminated HSV infection (N=186) Kimberlin et al. Pediatrics 2001; 108:223-229
Herpes Simplex Virus and SBI in Febrile Infants Herpes Simplex Virus (HSV) Checklist YES NO O O History of maternal HSV O O History of maternal fever at labor and delivery O O History of seizures or seizures during the evaluation O O Ill appearing infant O O Hypothermia present O O Vesicles on skin exam (including scalp) O O CSF with pleocytosis for age O O Thrombocytopenia O O Elevated transaminases (if obtained)
Herpes Simplex Virus and SBI in Febrile Infants: Conclusion If any item of the HSV checklist is present: RECOMMEND A thorough HSV evaluation be completed Empiric treatment with acyclovir (20 mg/kg) tid HSV Evaluation and Empiric Treatment * CSF HSV PCR * Nasopharyngeal, eye, and rectal viral swabs * Liver function tests specifically evaluating transaminases * Acyclovir at 20 mg/kg/dose every 8 hours
What is a Febrile Infant? Ages 29 60 (?90) days of life Similar pathogens to previous group Limited Listeria infection risk Late onset GBS Limited number of herpes infections after 4 weeks of age
Background: Febrile Young Infants Evaluation of febrile infants studied for decades 1% of all pediatric ED visits CMH ~650/year; national ~1% all visits Significant burden to hospital resources & society
Bachur 2001
SBI in low risk patients (%) Febrile Infant Protocols: Reported Statistics Sensitivity 92% Rochester Philadelphia Boston 1.1% 0.4% 5.4% (83-97) Specificity 50% (47-53) PPV 12.3% (10-16) NPV 98.9% (97-100) - Bachur. Pediatrics. 2001; 108; 311-316 98% (92-100) 42% (38-46) 14% (11-17) 99.7% (98-100) N/A 94.6% N/A N/A
Febrile Infant Protocols: Reported Statistics Rochester Philadelphia Boston SBI in low risk patients (%) 1.1% 0.4% 5.4% Sensitivity 92% (83-97) Specificity 50% (47-53) PPV 12.3% (10-16) NPV 98.9% (97-100) - Bachur. Pediatrics. 2001; 108; 311-316 98% (92-100) 42% (38-46) 14% (11-17) 99.7% (98-100) N/A 94.6% N/A N/A
Presumptive Failure Rates of Low-Risk FYI Protocols Boston 54/1000 (5.4%) NPV 94.6% (95% CI 92,96) Philadelphia 3.5/1000 (0.4%) NPV 99.7% (95% CI 98,100) -Pediatrics. 1999; 103; 627-631
Low Risk Febrile Infant Checklist Low Risk Febrile Infant Checklist YES NO O O Well appearing infant O O Previously healthy with no previous antibiotic use O O WBC between 5,000 and 15,000 O O Absolute Immature Granulocyte Count less than 0.04 x 10 3 / mcl or Band to Neutrophil ratio of less than 0.2 O O UA with less than 5 WBC/hpf and no Nitrites O O CSF with less than 8 WBC/hpf O O Chest x-ray (if obtained) with no focal infiltrate
CMH Febrile Infant CPG Requires full sepsis evaluation RSV exception Disposition up to evaluating MD and primary physician if patient is determined to be low-risk
RSV+ and Risk of SBI Does RSV positive status lower the risk of SBI? Retrospective cohort FYI (N=174) RSV+/SBI+ 2/174 (1.2%) Both UTI RSV-/SBI+ 22/174 (12.6%) UTI 17/22 Titus et al Pediatrics. 2003; 112:282-284
Respiratory Syncytial Virus and SBI in Febrile Infants Prospective, cross-sectional study (N=1248) RSV+ (n= 269) 17 (~7.0%) UTI: 14 (~5.4%) Bacteremia: 3 (~1.1%) All 3 < 29 days Bacterial Meningitis: 0 (0%) RSV- (n= 979) 116 (~12.5%) UTI: 98 (~10.1%) Bacteremia: 8 (~2.3%) Bacterial Meningitis: 8 (~0.9%) Levine et al Pediatrics. 2004; 1728-1734.
RSV + and Risk of SBI: Limitations Only 411 (33%) 28 DOL RSV+/SBI+: 8/82 (10.1%) 5 UTI s, 3 Bacteremia RSV-/SBI+: 47/329 (14.2%) Levine et al Pediatrics. 2004; 1728-1734.
Respiratory Syncytial Virus and SBI in Febrile Infants Statistically lower (but still clinically important) rates of UTI 3 bacteremia all in < 29 DOL 0 cases of meningitis Not powered to detect a difference in bacteremia or meningitis
Recommendations Full sepsis evaluation if the patient is ill appearing Blood culture and urine culture/ua with microscopy in all febrile infants less than 29 days Admit Hold antibiotics unless UAM positive UA with microscopy and urine culture in all febrile infants 29 60 days Hold antibiotics Disposition based on RSV CPG
Influenza and Risk of SBI Retrospective, cross-sectional study (N=705; 0-36 months old) Influenza positive (N=163) SBI rate 3/163 (1.8%) 2 UTI, 1 bacteremia, 0 meningitis Odds ratio of SBI and Influenza 0.14 Influenza negative (N=542) SBI rate 65/542 (12.0%) 38 UTI, 23 bacteremia, 4 meningitis Limitations Insufficient number of <29 DOL (13 +, 49 -) Smitherman et al Pediatrics 2005; 115:710-718
Influenza and Risk of SBI Multicenter, prospective, cross-sectional study N=1091; 0 to 60 DOL Influenza positive (N=123/844) [14.3%] SBI rate 3/119 (2.5%) 3 UTI, 0 bacteremia, 0 meningitis Influenza negative (N=721/844) [85.7%] SBI rate 92/690 (13.3%) 77 UTI, 16 bacteremia, 6 meningitis Relative Risk of SBI and Influenza 0.19 [0.06-0.59] Limitations Number of febrile neonates (268 <29 DOL, 541 29-60 DOL) Not powered for bacteremia/meningitis detection Krief et al Pediatrics 2009; 124(1): 30-9
Current Data on FYI with Documented Influenza Influenza positive febrile young infants (29-60 days of life) have a significantly lower risk of SBI than influenza negative FYI. Limited data on febrile neonates Currently, all influenza+ infants at least need UA and urinary cultures (+/- blood culture)
Conclusions Important to perform a full diagnostic evaluation in all febrile young infants No component of the screening assessment can be omitted Management without antibiotics of febrile illnesses can be safely accomplished in selected infants